Neuroimaging and Neuropsychological Outcomes in Urea Cycle Disorders
In proximal urea cycle disorders (UCD), particularly ornithine transcarbamylase deficiency (OTCD), hyperammonemia (HA) causes increased brain glutamine (Gln) which perturbation is thought to be at the core of the neurological injury. In contrast, in distal UCD such as citrullinemia (argininosuccinate synthetase deficie
| Condition(s) | Urea Cycle Disorders |
|---|---|
| Status | Recruiting |
| Study type | Observational |
| Summary | In proximal urea cycle disorders (UCD), particularly ornithine transcarbamylase deficiency (OTCD), hyperammonemia (HA) causes increased brain glutamine (Gln) which perturbation is thought to be at the core of the neurological injury. In contrast, in distal UCD such as citrullinemia (argininosuccinate synthetase deficiency; (ASSD) and argininosuccinic aciduria (argininosuccinate lyase deficiency); (ASLD) cognitive impairment and neuropsychiatric disease are common even in the absence of acute HA. As a consequence, both citrulline and argininosuccinate (ASA) or their metabolic products have been implicated as neurotoxic. In this project the investigators will use state-of- the-art neuroimaging and neuropsychological methods to investigate whether patients with OTCD have chronically elevated |
| Who can participate | Inclusion Criteria: Inclusion criteria for group 1: 1. Confirmed diagnosis of ornithine transcarbamylase deficiency (OTCD) by genetic analysis (genotype) and/or enzyme analysis with at least a single episode of HA hyperammonemic (HA) encephalopathy 2. Ability to undergo MRI without sedation 3. Ages 7 - 50 years 4. Ability to provide informed consent or assent to the procedures 5. Healthy controls (age and gender matched) Inclusion criteria for group 2: 1. Males and females with a UCD who are having an acute metabolic crisis, with ammonia levels between 100-300 µM 2. Subjects must be awake, and not comatose and able to maintain patent airway on their own and in the opinion of the examining physician, medically stable without risk for acute decompensation and must continue to be stable based |
| Ages | 7 Years to 50 Years |
| Sex | All |
| Accepts healthy volunteers | Yes |
| Lead sponsor | Children's National Research Institute |
| Locations | Washington D.C., District of Columbia, United States |
| Start date | 2016-08 |
| NCT ID | NCT02935283 |
| Official listing | https://clinicaltrials.gov/study/NCT02935283 |